A pharmacokinetic study of amoxycillin in febrile beagle dogs following repeated administrations of endotoxin

• Published in: Journal of veterinary pharmacology and therapeutics Vol. 24; no. 6; pp. 379 - 383
• Main Authors: Marier, J.-F., Beaudry, F., Ducharme, M. P., Fortin, D., Moreau, J.-P., Massé, R., Vachon, P.
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01-12-2001
• Subjects: Administration, Oral; Amoxicillin - administration & dosage; Amoxicillin - blood; Amoxicillin - pharmacokinetics; Amoxicillin - therapeutic use; Animals; Area Under Curve; Chromatography, High Pressure Liquid - veterinary; Dog Diseases - drug therapy; Dogs - metabolism; Escherichia coli; Escherichia coli Infections - chemically induced; Escherichia coli Infections - drug therapy; Escherichia coli Infections - veterinary; Fever - chemically induced; Fever - drug therapy; Fever - veterinary; Lipopolysaccharides - administration & dosage; Male; Penicillins - administration & dosage; Penicillins - blood; Penicillins - pharmacokinetics; Penicillins - therapeutic use
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1046/j.1365-2885.2001.00359.x

The pharmacokinetics of amoxycillin was studied in nine male beagle dogs under healthy and febrile conditions. In Period 1, dogs received 20 mg/kg of an oral suspension of amoxycillin. Intravenous doses of saline, 2 and 20 μg/kg of endotoxin (LPS from Escherichia coli serotype) were administered to dogs (three per group) prior to administration of 20 mg/kg of amoxycillin in Period 2. Rectal temperature and behavioral changes were recorded and blood samples were collected over 12 h for pharmacokinetic analysis. Amoxycillin was assessed in plasma using liquid chromatography coupled with mass spectrometry. Plasma concentrations were analysed using a one‐compartment model with lag‐time for absorption using an iterative two‐stage method. As compared with control groups, amoxycillin clearance decreased significantly with preliminary treatments of 2 μg/kg endotoxin (0.209 vs. 0.140 L/h kg, P < 0.05) and 20 μg/kg endotoxin (0.214 vs. 0.075 L/h kg, P < 0.05). As a result of this, the area under curve for the 2 and 20 μg/kg endotoxin groups increased significantly 100.4 vs. 149.4 μg h/mL (P < 0.05) and 99.2 vs. 277.7 μg h/mL (P < 0.05), respectively. Other drugs currently used for the treatment of fever and septic shock should be re‐evaluated using a febrile animal model to avoid improper dose administration.